Studies are being performed on the relationship of the energy status of the hippocampal slice to synaptic transmission in the region of the dentate gyrus. Creatine and the cyclic analog, cyclocreatine, were added to the incubation medium for various periods of time and the concentration of creatine phosphate and cyclocreatine phosphate were determined. The perforant pathway axons were stimulated and the activity recorded in the region of the dentate gyrus during an anoxic insult. In the creatine studies, the loss of signal was delayed during anoxia which was attributed to a significant increase in the levels of phosphocreatine. At both 5 and 25 mM cyclocreatine, there was evidence of seizure discharge under normoxic conditions. In spite of this, the cyclocreatine still prolonged neuronal function during the anoxic challenge. Thus, increasing the pool of energy reserves in the brain may prolong brain function during a variety of insults.